A Novel Animal Model for Autoimmune Orchitis: Therapeutic Efficacy of a PLGA-Based Polymeric Nano-Formulation with Full Histopathological Characterization

Introduction: Autoimmune Orchitis (AO) is an immune-mediated disorder of the male urogenital system that leads to impaired spermatogenesis, endocrine disruption, and subfertility. Current experimental models insufficiently capture organ-spanning pathology and translational therapeutic responsiveness. To establish a reproducible, system-integrated animal model of AO and to evaluate the therapeutic efficacy of a bioengineered nano-formulation (BNF) with comprehensive histopathological characterization across the male urogenital tract. Methods: Adult male rodents underwent a staged AO induction paradigm designed to elicit synchronized inflammation of the testis, epididymis, accessory sex glands, and secondary urinary tract structures. Animals were randomized into Control, AO, AO+Vehicle, and AO+BNF groups. Clinical indices, reproductive outcomes, serum and tissue biomarkers, and full-spectrum histopathology (testes, epididymides, prostate, seminal vesicles, urinary bladder, kidneys) were assessed. Results: The model consistently produced lymphoplasmacytic orchitis with seminiferous epithelial collapse, epididymal ductal obstruction, stromal inflammation of accessory glands, and secondary inflammatory changes in the bladder and kidneys. BNF significantly reduced inflammatory burden, preserved urogenital architecture, improved sperm quantity and quality, normalized accessory gland morphology, and attenuated downstream urinary pathology (P-value<۰.۰۵). Conclusions: This novel AO model enables integrated evaluation of urogenital autoimmunity and demonstrates robust therapeutic benefit of BNF, supporting translational relevance for autoimmune-mediated male infertility.

کلیدواژه ها:

Autoimmune orchitis ، animal model ، nano-formulation ، male urogenital system ، histopathology ، Translational Urology